To estimate the prevalence of oral high-risk human papillomavirus (hr-HPV) infection and the proportion of hr-HPV–related oropharyngeal squamous cell carcinoma (OPSCC) among Indigenous and non-Indigenous populations.
Data Source
Electronic database searches of PubMed, PubMed Central, Embase, MEDLINE, Scope, and Google Scholar were conducted for articles published from January 2000 until November 2019.
Review Methods
Studies were included with a minimum of 100 cases assessing hr-HPV infection in either population samples or oropharyngeal cancer tumor series. The objective was to conduct meta-analyses to calculate the pooled prevalence of oral hr-HPV infection by adjusting for age group or sex in primary studies, the incidence of OPSCC, and the proportion of hr-HPV–related OPSCC in Indigenous people and non-Indigenous/general populations.
Results
We identified 47 eligible studies from 157 articles for meta-analyses. The pooled prevalence of oral hr-HPV infection was 7.494% (95% CI, 5.699%-9.289%) in a general population, with a higher prevalence among men (10.651%) than women (5.176%). The pooled incidence rate was 13.395 (95% CI, 9.315-17.475) and 7.206 (95% CI, 4.961-9.450) per 100,000 person-years in Indigenous and non-Indigenous populations, respectively. The overall pooled proportion of hr-HPV–related OPSCC was 50.812% (95 CI, 41.656%-59.969%). The highest proportion was in North America (60.221%), while the lowest proportion was in the Asia-Pacific (34.246%).
Conclusion
Our findings suggest that in the general population, the prevalence of oral hr-HPV infection is lower among females and those in younger age groups. The incidence of OPSCC was higher among Indigenous than non-Indigenous populations, with the proportion being highest in North America.
GuptaBJohnsonNWKumarN.Global epidemiology of head and neck cancers: a continuing challenge. Oncology. 2016;91:13-23.
2.
RazzaghiHSaraiyaMThompsonTDHenleySJViensLWilsonR.Five-year relative survival for human papillomavirus–associated cancer sites. Cancer Cytopathol. 2018;124:203-211.
3.
MoroJDSMaronezeMCArdenghiTMBarinLMDanesiCC. Oral and oropharyngeal cancer: epidemiology and survival analysis. Einstein (Sao Paulo). 2018;16:eAO4248.
4.
MenaMTabernaMMonfilL, et al. Might oral human papillomavirus (HPV) infection in healthy individuals explain differences in HPV-attributable fractions in oropharyngeal cancer? A systematic review and meta-analysis. J Infect Dis. 2019;219:1574-1585.
5.
ChaturvediAKAndersonWFLortet-TieulentJ, et al. Worldwide trends in incidence rates for oral cavity and oropharyngeal cancers. J Clin Oncol. 2013;31:4550-4559.
6.
HongAMLeeCSJonesD, et al. Rising prevalence of human papillomavirus–related oropharyngeal cancer in Australia over the last 2 decades. Head Neck. 2016;38(5):743-750.
7.
SteinauMSaraiyaMGoodmanMT, et al. Human papillomavirus prevalence in oropharyngeal cancer before vaccine introduction, United States. Emerg Infect Dis. 2014;20:822-828.
8.
Lang KuhsKAKreimerARTrivediS, et al. Human papillomavirus 16 E6 antibodies are sensitive for human papillomavirus–driven oropharyngeal cancer and are associated with recurrence. Cancer. 2017;123:4382-4390.
MarurSD’SouzaGWestraWHForastiereAA.HPV-associated head and neck cancer: a virus-related cancer epidemic. Lancet Oncol. 2010;11:781-789.
11.
SchiffmanMCliffordGBuonaguroFM.Classification of weakly carcinogenic human papillomavirus types: addressing the limits of epidemiology at the borderline. Infect Agent Cancer. 2009;4:8.
12.
JiangYHanleyBBrassardP, et al. Human papillomavirus infection and the association with abnormal Pap findings in Yukon, Canada. J Low Genit Tract Dis. 2013;17:346-353.
13.
RaymondSLiuBTaioliE.Racial differences in the prevalence of oncogenic oral human papillomavirus infection types in the United States adult population. Head Neck. 2018;40:2219-2227.
StephensCNettletonCPorterJWillisRClarkS.Indigenous peoples’ health—why are they behind everyone, everywhere?Lancet. 2005;366:10-13.
16.
MazereeuwMVWithrowDRNishriEDTjepkemaMVidesEMarrettLD.Cancer incidence and survival among Metis adults in Canada: results from the Canadian census follow-up cohort (1992-2009). CMAJ. 2018;190:E320-E326.
17.
ValeryPCCooryMStirlingJGreenAC.Cancer diagnosis, treatment, and survival in Indigenous and non-Indigenous Australians: a matched cohort study. Lancet. 2006;367:1842-1848.
18.
ShahidSThompsonSC.An overview of cancer and beliefs about the disease in Indigenous people of Australia, Canada, New Zealand and the US. Aust N Z J Public Health. 2009;33:109-118.
19.
LiberatiAAltmanDGTetzlaffJ, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. PLoS Med. 2009;6:e1000100.
20.
EggerMSmithGDMinderC.Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997;31:629.
HanssonBGRosenquistKAntonssonA, et al. Strong association between infection with human papillomavirus and oral and oropharyngeal squamous cell carcinoma: a population-based case-control study in southern Sweden. Acta Otolaryngol. 2005;125:1337-1344.
23.
RaginCEdwardsRLarkins-PettigrewM, et al. Oral HPV infection and sexuality: a cross-sectional study in women. Int J Mol Sci. 2011;12:3928-3940.
24.
ChenKMStephenJKGhanemT, et al. Human papilloma virus prevalence in a multiethnic screening population. Otolaryngol Head Neck Surg. 2013;148:436-442.
25.
NordforsCGrunNHaeggblomL, et al. Oral human papillomavirus prevalence in high school students of one municipality in Sweden. Scand J Infect Dis. 2013;45(11):878-881.
26.
Colon-LopezVQuinones-AvilaVDel Toro-MejiasLM, et al. Oral HPV infection in a clinic-based sample of Hispanic men. BMC Oral Health. 2014;14:7.
27.
NakashimaKShigeharaKKawaguchiS, et al. Prevalence of human papillomavirus infection in the oropharynx and urine among sexually active men: a comparative study of infection by papillomavirus and other organisms, including Neisseria gonorrhoeae, Chlamydia trachomatis, Mycoplasma spp, and Ureaplasma spp. BMC Infect Dis. 2014;14:43.
28.
BuiTCTranLTMarkhamCM, et al. Self-reported oral health, oral hygiene, and oral HPV infection in at-risk women in Ho Chi Minh City, Vietnam. Oral Surg Oral Med Oral Pathol Oral Radiol. 2015;120:34-42.
29.
UkenRBBrummerOvon Schubert-BayerCBrodeggerTTeudtIU.Oral HPV prevalence in women positive for cervical HPV infection and their sexual partners: a German screening study. Eur Arch Otorhinolaryngol. 2016;273:1933-1942.
30.
CiccareseGHerzumAReboraADragoF.Prevalence of genital, oral, and anal HPV infection among STI patients in Italy. J Med Virol. 2017;89:1121-1124.
31.
LupatoVHolzingerDHoflerD, et al. Prevalence and determinants of oral human papillomavirus infection in 500 young adults from Italy. PLoS One. 2017;12:e0170091.
32.
KiwerskaKJozefiakAMarkowskaJKedziaWJackowskaJWierzbickaM.Oral-genital human papillomavirus infection in Polish couples: frequent detection of HPV 42. BMC Infect Dis. 2019;19:122.
33.
RolloFPichiBBenevoloM, et al. Oral testing for high-risk human papillomavirus DNA and E6/E7 messenger RNA in healthy individuals at risk for oral infection. Cancer. 2019;125:2587-2593.
34.
SchlechtNFMasikaMDiazA, et al. Risk of oral human papillomavirus infection among sexually active female adolescents receiving the quadrivalent vaccine. JAMA Netw Open. 2019;2:e1914031.
35.
KellyJJLanierAPAlbertsSWigginsCL.Differences in cancer incidence among Indians in Alaska and New Mexico and US Whites, 1993-2002. Cancer Epidemiol Biomarkers Prev. 2006;15:1515-1519.
36.
CarriereGMTjepkemaMPennockJGoedhuisN.Cancer patterns in Inuit Nunangat: 1998-2007. Int J Circumpolar Health. 2012;71:18581.
37.
FrydrychAMSlack-SmithLMParsonsRThrelfallT.Oral cavity squamous cell carcinoma—characteristics and survival in aboriginal and non-aboriginal Western Australians. Open Dent J. 2014;8:168-174.
38.
ChelimoCElwoodJM.Sociodemographic differences in the incidence of oropharyngeal and oral cavity squamous cell cancers in New Zealand. Aust N Z J Public Health. 2015;39:162-167.
39.
EricksonBBironVLZhangHSeikalyHCoteDW.Survival outcomes of First Nations patients with oral cavity squamous cell carcinoma (Poliquin 2014). J Otolaryngol Head Neck Surg. 2015;44:4.
40.
SettleKPosnerMRSchumakerLM, et al. Racial survival disparity in head and neck cancer results from low prevalence of human papillomavirus infection in black oropharyngeal cancer patients. Cancer Prev Res (Phila). 2009;2:776-781.
41.
AngKKHarrisJWheelerR, et al. Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med. 2010;363:24-35.
42.
HongADobbinsTLeeCS, et al. Relationships between epidermal growth factor receptor expression and human papillomavirus status as markers of prognosis in oropharyngeal cancer. Eur J Cancer. 2010;46:2088-2096.
43.
HockingJSSteinAConwayEL, et al. Head and neck cancer in Australia between 1982 and 2005 show increasing incidence of potentially HPV-associated oropharyngeal cancers. Br J Cancer. 2011;104:886-891.
44.
RotnáglováETachezyRSalákováM, et al. HPV involvement in tonsillar cancer: prognostic significance and clinically relevant markers. Int J Cancer. 2011;129:101-110.
45.
St GuilyJLJacquardACPrétetJL, et al. Human papillomavirus genotype distribution in oropharynx and oral cavity cancer in France—the EDiTH VI study. J Clin Virol. 2011;51:100-104.
46.
GavidMPilletSPozzettoB, et al. Human papillomavirus and head and neck squamous cell carcinomas in the south-east of France: prevalence, viral expression, and prognostic implications. Acta Otolaryngol. 2013;133:538-543.
47.
WallineHMKomarckCMcHughJB, et al. High-risk human papillomavirus detection in oropharyngeal, nasopharyngeal, and oral cavity cancers comparison of multiple methods. JAMA Otolaryngol Head Neck Surg. 2013;139:1320-1327.
48.
NordforsCGrünNTertipisN, et al. CD8+ and CD4+ tumour infiltrating lymphocytes in relation to human papillomavirus status and clinical outcome in tonsillar and base of tongue squamous cell carcinoma. Eur J Cancer. 2013;49:2522-2530.
49.
RietbergenMMLeemansCRBloemenaEHeidemanDABraakhuisBJHesselinkAT.Increasing prevalence rates of HPV attributable oropharyngeal squamous cell carcinomas in the Netherlands as assessed by a validated test algorithm. Int J Cancer. 2013;132:1565-1571.
50.
HamaTTokumaruYFujiiM, et al. Prevalence of human papillomavirus in oropharyngeal cancer: a multicenter study in Japan. Oncology (Switzerland). 2014;87:173-182.
51.
WilsonDDCrandleyEFSimA, et al. Prognostic significance of p16 and its relationship with human papillomavirus in pharyngeal squamous cell carcinomas. JAMA Otolaryngol Head Neck Surg. 2014;140:647-653.
52.
HennemanRVan MonsjouHSVerhagenCVM, et al. Incidence changes of human papillomavirus in oropharyngeal squamous cell carcinoma and effects on survival in the Netherlands Cancer Institute, 1980-2009. Anticancer Res. 2015;35:4015-4022.
53.
NasmanANordforsCHolzhauserS, et al. Incidence of human papillomavirus positive tonsillar and base of tongue carcinoma: a stabilisation of an epidemic of viral induced carcinoma?Eur J Cancer. 2015;51:55-61.
54.
D’SouzaGAnantharamanDGheitT, et al. Effect of HPV on head and neck cancer patient survival, by region and tumor site: a comparison of 1362 cases across three continents. Oral Oncol. 2016;62:20-27.
55.
MirghaniHCasiraghiOGuerlainJ, et al. Diagnosis of HPV driven oropharyngeal cancers: comparing p16 based algorithms with the RNAscope HPV-test. Oral Oncol. 2016;62:101-108.
56.
SaitoYAndoMFujimotoC, et al. Human papillomavirus 16 physical status and the TP53 Codon 72 polymorphism in Japanese HPV-positive oropharyngeal cancer patients. ORL J Otorhinolaryngol Relat Spec. 2016;78:46-54.
57.
FeinsteinAJShaySGChangELewisMSWangMB.Treatment outcomes in veterans with HPV-positive head and neck cancer. Am J Otolaryngol. 2017;38:188-92.
58.
LiederbachEKyrillosAWangCHLiuJCSturgisEMBhayaniMK.The national landscape of human papillomavirus–associated oropharynx squamous cell carcinoma. Int J Cancer. 2017;140:504-512.
59.
SmithEAKumarBKomurovK, et al. DEK associates with tumor stage and outcome in HPV16 positive oropharyngeal squamous cell carcinoma. Oncotarget. 2017;8:23414-23426.
60.
JouhiLHalmeEIrjalaH, et al. Epidemiological and treatment-related factors contribute to improved outcome of oropharyngeal squamous cell carcinoma in Finland. Acta Oncol. 2018;57:541-551.
61.
MengHXMiaoSSChenK, et al. Association of p16 as prognostic factors for oropharyngeal cancer: evaluation of p16 in 1470 patients for a 16 year study in northeast China. Biomed Res Int. 2018;2018:9594568.
62.
RietbergenMMvan BokhovenALissenberg-WitteBI, et al. Epidemiologic associations of HPV-positive oropharyngeal cancer and (pre)cancerous cervical lesions. Int J Cancer. 2018;143:283-288.
63.
RasmussenJHGronhojCHakanssonK, et al. Risk profiling based on p16 and HPV DNA more accurately predicts location of disease relapse in patients with oropharyngeal squamous cell carcinoma. Ann Oncol. 2019;30:629-636.
64.
VawdaNBanerjeeRNDebenhamBJ.Impact of smoking on outcomes of HPV-related oropharyngeal cancer treated with primary radiation or surgery. Int J Radiat Oncol Biol Phys. 2019;103:1125-1131.
65.
BorensteinMHedgesLHigginsJRothsteinHR.Identifying and Quantifying Heterogeneity: Introduction to Meta-analysis. John Wiley & Sons; 2009:107-25.
66.
BorensteinMHigginsJPHedgesLVRothsteinHR.Basics of meta-analysis: I(2) is not an absolute measure of heterogeneity. Res Synth Methods. 2017;8:5-18.
67.
JamiesonLMAntonssonAGarveyG, et al. Prevalence of oral human papillomavirus infection among Australian Indigenous adults. JAMA Netw Open. 2020;3:e204951.
68.
BermanTASchillerJT.Human papillomavirus in cervical cancer and oropharyngeal cancer: one cause, two diseases. Cancer. 2017;123:2219-2229.
69.
WhopLJGarveyGBaadeP, et al. The first comprehensive report on Indigenous Australian women’s inequalities in cervical screening: a retrospective registry cohort study in Queensland, Australia (2000-2011). Cancer. 2016;122:1560-1569.
70.
BrothertonJMWinchKLChappellG, et al. HPV vaccination coverage and course completion rates for Indigenous Australian adolescents, 2015. Med J Aust. 2019;211:31-36.
71.
HedgesJGarveyGJuX, et al. Reflections from fieldnotes: an oral HPV infection and oropharyngeal cancer study among Indigenous Australians. Med J Aust. In press.
72.
DavyCHarfieldSMcArthurAMunnZ, et al. Access to primary health care services for Indigenous peoples: a framework synthesis. Int J Equity Health. 2016;15:163.
73.
JamiesonLGarveyGHedgesJ, et al. Human papillomavirus and oropharyngeal cancer among indiegenous australians: protocol a prevalence study of oral-related human papillomavirus and cost-effectiveness of prevention. JMIR Res Protoc. 2018;7:e10503.
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